Effects of Nicotine on Brain Activity as Measured by fMRI: Investigation of the pharmacodynamics of nicotine in the brain using pharmacological MRI to look at the effect of varying the rate, number of injections and timing of multiple injections on neuronal activation. We have completed 11 scan sessions however, data analysis is dependent on more participants.[unreadable] [unreadable] Effects of Nicotine on Cognitive Task Performance and Brain Activity as Measured by fMRI: The effects of transdermal nicotine in a selective-divided attention task were assessed. Increased brain activation with divided attention conditions was observed in controls in a range of frontoparietal and visual cortical areas. This increase may reflect additional processing demands when introducing a secondary task that does not differ qualitatively from processes of selective attention. [unreadable] [unreadable] Data from smokers and controls performing an intention-attention task have been analyzed. Neither nicotine nor placebo had a significant effect on reaction time, but a significant effect of nicotine on accuracy was noted. This effect was accompanied by a differential effect of nicotine on brain response to the different primes in multiple regions. The supramarginal gyrus, striatum, and occipital lobe demonstrated a significant nicotine-dependent increase in response to intentional primes. This suggests that behavioral effects of acute nicotine in smokers can be characterized by attention and intention. This effect on intention appears to be mediated by a nicotinic facilitation of function in regions associated with motor intention. [unreadable] [unreadable] fMRI was used to ascertain changes in neural function associated with reward processing following acute nicotine administration. Preliminary data indicated a differential response in areas of the brain associated with reward processing, between smokers and controls, which appear to be modulated by acute nicotine administration. Recruitment is ongoing and experimental completion is projected within 6 months. [unreadable] [unreadable] Automatic versus Evaluative Components of Cue Reactivity: The aim of this project is to dissociate components of cue reactivity by embedding drug-related pictures into different versions of the N-back task, thus varying the amount of processing resources available for picture processing. Pilot results from overnight-deprived smokers and non-smokers suggest there are two components of cue reactivity. The first is dependent on availability of processing resources and is associated with autonomic arousal. The second does not compete for processing resources and is negatively associated with craving, with a trend toward a positive relationship with actual smoking behavior. This behavioral experiment is being repeated using fMRI in hopes of identifying neural mediators for each of these components. [unreadable] [unreadable] Nicotinic effect on the neurophysiology of Schizophrenia: This collaborative, double-blind, placebo-controlled study aims to identify nicotine effects on neurophysiogoical functions in eye movement and attention by comparing behavior and fMRI activation in schizophrenics and healthy controls. Our aim is to identify brain regions involved in nicotine-induced change during eyetracking, anticipatory learning of eye movement, sustained attention, and resting state between schizophrenics and controls. Preliminary analysis identified resting state functional connectivity of the cingulate circuitry that differentiates between groups and between nicotine and placebo conditions. Data analysis for eye movement and sustained attention tasks is underway.[unreadable] [unreadable] Reward processing in cocaine addiction: fMRI is employed to ascertain the function of neural systems in response to cocaine and the role that they play in processing rewarding stimuli while being drug-free or under acute cocaine influence. Participant recruitment was temporarily placed on hold due to the closing of the NIDA IRP overnight facility and is planned to resume pending approval of another overnight facility.[unreadable] [unreadable] Dopamine function and reward processing in Schizophrenia: We examined brain activity related to reinforcement processing in schizophrenia and the contributions of dopamine system dysfunction to schizophrenic psychopathology. We administered two behavioral paradigms involving reward processing to schizophrenics and controls in an MRI scanner to elicit brain responses to reinforcement, stimuli predictive of reinforcement, or the surprising omission of reinforcement. Our data as well as previous studies indicate that when reinforcement (juice) is delivered at unexpected times, controls show activation in the left putamen and left nucleus accumbens, both targets of brain dopamine systems. These activations were absent in schizophrenics, suggests that they do not exhibit the customary neural correlate of prediction errors. [unreadable] [unreadable] Neurophysiological phenotypes in Schizophrenia: Smooth pursuit eye movement (SPEM) abnormalities are among the most reproducible biological findings associated with schizophrenia. The neural base of reported abnormalities in SPEM is not clear, and little is known about how genetic effects are translated into aberrant neural circuit controlling SPEM. In this collaborative protocol we employ fMRI to examine perceptual and cognitive contributions to cortical mechanisms controlling eye movement outputs. Schizophrenics, full siblings of schizophrenics, and healthy controls with no family history of psychosis are being studied. The sibling group also allows examination of SPEM dysfunction in individuals not affected by antipsychotic medications. 6 participants are currently enrolled.[unreadable] [unreadable] Effect of functional genetic polymorphisms on brain morphology and function: The aim of this study is to integrate genotyping with structural and functional brain imaging to investigate the impact of specific functional polymorphisms on morphology and function of amygdala and hippocampus and on behavior mediated by these brain regions. Participants perform two tasks an emotional memory task, which is performed in the scanner; and a reward task outside the MRI. Preliminary data analysis from 19 participants is underway. Thus far, the results show significant activity in the amygdala and the hippocampus, which is consistent with previous findings. [unreadable] [unreadable] The neural basis of cue-elicited cigarette craving and its control: The goal of this study is to ascertain the neural basis of cue-elicited cigarette craving and its control in smokers. Subjects participate in five inpatient and three outpatient sessions where fMRI-compatible EEG and real-time feedback fMRI will be implemented. Recruitment has been slow (with only 1 participant scheduled) in part due to the requirement that subjects be regular cigarette smokers interested in quitting smoking in the near future but are not current abstainers. [unreadable] [unreadable] Prenatal drug exposure: effects on the adolescent brain and behavior bevelopment. This collaborative study looks at the effects of intrauterine drug exposure on cognitive and reward system function in adolescents. Subjects will perform a visuospatial working memory task and a gambling task with wins and losses while undergoing fMRI. Resting data and DTI will be obtained. [unreadable] [unreadable] Brain activity alterations as aeasured by fMRI during nicotine self-administration: We examine neural underpinnings of nicotine self-administration. fMRI data will allow examination of the choice to self-administer, the response to a self-administered injection, response to cues associated with nicotine and response to delays of drug delivery